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Catching Up On Creatine


Back in college, when I first started my romance with the iron, I knew pretty much nothing about sports nutrition. Nor did anyone else I knew. For the first two or three years I lifted, I didn't even consider post-workout shakes.

Ridiculous, I know.

Some of the guys back then were using creatine, taking in 20 grams a day and extolling its virtues. Others equated creatine with steroids — which could be good or bad, depending on who was making the comparison. And some doctors told me it would destroy my kidneys.

More recently, doctors have tempered their stance, and recognize that creatine can be vital in the maintenance of health; it's even used as a form of medical therapy for people with neurologic and muscle pathologies. Physicians involved in training athletes are familiar with the benefits of creatine, and most of them have largely positive opinions of the substance.

But doctors, as I mentioned in this article, are not scientists. That's why their views of creatine are still cautious and conditional, with warnings about muscle cramps, tendon tears, GI upset, and kidney problems.

I'm a few weeks away from becoming a doctor, but I came to medicine with scientific training. (I specialized in the study of the sexual and reproductive habits of small South American monkeys. I know more about monkey love than just about anybody on the planet who's not an actual monkey.) That background helped me investigate all of the above medical issues before I decided to try creatine for myself about a year ago.

I take in nowhere near 20 grams a day, and I've never had so much as a cramp. Any muscle tears I've inflicted on myself have been due to training idiocy, not the fine white powder I now swear by.

That said, even in the lifting community you'll find a lot of creatine-related myths and misconceptions in terms of how it works, how much to take, and what kind to use. Even the casual acceptance of creatine's harmlessness isn't merited. Doctors aren't entirely wrong when they warn about musculoskeletal issues.

So even though creatine is considered a settled issue in gym culture — it's safe, it's simple to use, it works — there's probably a lot about it you don't know. Even if you're currently using it, you may still be using more than you need, or not getting all the benefits you could from it.

And if you're not using it at all? After reading this, you'll probably want to start.


Physiology

Fundamentals first:

Here's why:

So what matters is the addition or removal of a phosphate group. It happens all day, every day, in every cell.

But there are times when your body can't keep up with energy demand, and it needs another source of phosphates. That's where creatine acts as a backup power generator, since most of the creatine in your body is bound to readily usable phosphate.

An enzyme called creatine kinase (CK) pulls the phosphate from creatine so it can hook up with ADP to make more ATP. The creatine-phosphate shunt, as it's called, is a much faster process than either aerobic or anaerobic metabolism, and thus allows your body to use energy faster and in greater amounts than it otherwise could.

The catch? It can only do this for a few seconds at a time. That's why, in theory, creatine supplementation should improve performance in anything requiring all-out expressions of speed, strength, and power.

The average person has about 1.7 grams of creatine per kilogram of body mass. (8) So a 200-pound man (90 kilograms) holds about 150 grams of creatine. But the maximum capacity is 2.3 grams per kilogram of body mass, or 210 grams in that same 200-pound guy. (11)

If there's an easy and safe way to increase the capacity of your body's backup battery by 40%, and if you had good reason to believe that increase would improve your performance in the gym or in your favorite sports, why wouldn't you do it?

Let's look at safety first.


Safety

Creatine is not toxic. Everyone agrees on that much. Some have argued that its byproduct, creatinine, is toxic. It's a complete falsehood, but it sounds just plausible enough to make it lucrative for companies to create fancy formulas to alleviate this imaginary danger.

Yes, doctors do use creatinine as a marker of kidney function. And, generally speaking, the higher your creatinine is, the more toxic waste products of metabolism you have in your system. But we have lots of research showing that creatinine itself isn't toxic, with the researchers injecting extreme amounts into human and animal subjects. (16) Creatinine just happens to be an excellent proxy for the bad stuff in people with already impaired kidney function.

However, the process of making creatine in a lab can create toxic byproducts, such as dicyandamide, dihydrotriazine, and even arsenic. (2) Because creatine isn't regulated by the FDA, you can't be sure of the purity or safety of the product, which is why staying away from the cheaper stuff is a matter of both common sense and self-preservation.

As with protein, you'll hear debates about possible kidney damage. Supplemental creatine does increase the amount of work the kidneys have to do, and we don't know the long-term effects of this. What we do know is that studies ranging from six months to five years have shown no detrimental effects of creatine supplementation with doses ranging from 3 to 20 grams per day. (17)


Side Effects

Almost all the side effects, in my opinion, have to do with the fact that creatine is hygroscopic, which basically means it acts like a sponge.

First, it moves into your gut, drawing water from surrounding tissues into the gastrointestinal tract. This can cause bloat, and even diarrhea, if some of the creatine isn't properly absorbed.

Once it's absorbed, creatine moves into your blood. Being hygroscopic, it has the potential to move water from inside your cellsto the blood. This tissue dehydration can predispose you to muscle cramps and even connective-tissue injury, due to the drying out of the tendons and ligaments. Once the creatine has moved into your muscle, it can move water from the blood into your tissue. This creates intravascular volume depletion, which can dehydrate you, put you at risk for kidney stones, and create another mechanism by which you might end up with connective-tissue injury.

The first step in avoiding these side effects is simple and economical: Don't take more than you need.

The second step is to avoid drinking creatine before you work out. The hygroscopic effects will predominate in either your gut (creating bloat and diarrhea) or your bloodstream (leaving you with dried-out muscles, tendons, and ligaments).

The third and probably most important step is to mix your creatine fully. Most of us, myself included, drink our creatine with some of the powder still visibly floating around in the water. At this point, even though you candrink it down, it hasn't fully dissolved. That means it's going to suck water from the places where water is supposed to be.

Mix it with enough water to dissolve it fully — and you'll be surprised by just how much water that takes — and you'll "saturate the sponge," so to speak.

Finally, it's worth mentioning that the fancier products, which I discuss in the next section, will most likely digest and be absorbed by your muscles quicker. Quicker absorption means reduced side effects from the bulk movement of water. But, to my knowledge, there is absolutely no literature indicating that this actuallyresults in decreased rate of side effects.


Monohydrate, Alpha-keto-glutarate, Ethyl-ester: What's the Difference?

There are a lot of different forms of creatine on the market. And pretty much everything aside from the old standby of creatine monohydrate (CM) is expensive. The more expensive forms, most notably creatine alpha-keto-glutarate (C-AKG) and creatine ethyl-ester (CEE), claim advantages in terms of stability and absorbability. The claims are probably true, but the more important question is, does this offer a substantial enough advantage to justify the price?

The first issue is stability. It's "common knowledge" that creatine is unstable in water and acid and will break down into useless creatinine. Which is why you shouldn't mix it with water until right before you drink it, and why you shouldn't mix it in acidic fluids like orange juice. And one of the justifications for the fancier products is that CM "won't survive the passage" through the highly acidic environment of the stomach.

I don't believe any of this. If creatine breaks down into useless creatinine after sitting in water for 10 minutes, how would any possibly get into your body? After all, it takes a while for the creatine you ingest to actually end up in your bloodstream. It's mixed in an aqueous solution for most of that time. And once it's digested, it's going to be in the watery solution known as blood. Followed by sitting in muscles that are made up of ... mostly water. Sure enough, studies have shown that even after being left in an aqueous solution for several weeks, a substantial portion of creatine remains in its biologically useful form. (3)

As for acid, orange juice has a pH of 3 to 4. That's fairly acidic. But compare that to your stomach, which has a pH of 2. That's somewhere between 10 and 100 times as acidic as orange juice. One study found that if exposed to a pH of 3.5 for three days, only about 21% of creatine breaks down into creatinine. Again, this makes perfect sense. If creatine were so unstable in acid, CM would never work, in anyone. Which hasn't exactly been what the research, or anyone's experience, has shown. (4)

So stability isn't really a concern.

Manufacturers of C-AKG and CEE also make the claim that their products are absorbed by the digestive tract and muscle tissue faster and more completely than plain old CM. This claim is more logical. You see, substances can be described as either hydrophilic or lipophilic. Without getting into too much boring detail, a hydrophilicsubstance dissolves in water (or blood) more readily. And a lipophilicsubstance passes through the cell membrane more easily.

Creatine monohydrate is very hydrophilic and not very lipophilic. CEE and C-AKG are much more lipophilic, and thus may offer an advantage in terms of how fast and how completely they're absorbed.

Does this offer any practical advantages? Well, as already touched upon, there seems to be an absolute ceiling of how much creatine we can store. Neither CEE nor C-AKG will raise this ceiling. And a preponderance of research studies indicates that most people can reach the maximum creatine density on a simple regimen of CM, 5 grams per day or less, with or without loading. (5, 6, 7)

On the other hand, most of the side effects, downsides, and injuries associated with creatine supplementation most likely have to do with just how hydrophilic it is, and the often lengthy time it takes to be absorbed — first by your digestive tract, then by your muscles. As I said earlier, though, these theoretical advantages of the more expensive products aren't backed up by any real-world testing.

Simply put, creatine monohydrate works just fine, and at a reasonable cost. Biotest's high-quality German micronized creatine monohydrate costs about $5 per month, as opposed to $15 to $20 for the others. While there are certain potential advantages to CEE and C-AKG, I don't find them compelling enough to throw down the extra cash.



Catching Up On Creatine

By increasing work capacity, creatine allows you to lift more weight for more reps.

Catching Up On Creatine

Nobody on the planet knows more about monkey sex than Nik.

Catching Up On Creatine

Energy in the body is produced, stored, exchanged, and used through the mediator ATP.

Biotest German Creatine

Catching Up On Creatine


New Kids on the Block: Creatine Citrate and Creatine Pyruvate

Unlike CEE and C-AKG, creatine citrate and creatine pyruvate (also known as creatine 2-oxopropanoate) have been embraced a bit more enthusiastically by the medical, nutritional, and scientific communities. Several researchers and physicians even recommend them for people taking creatine for therapeutic purposes. 

The key difference in the claims made for creatine citrate and pyruvate is that they offer complementary benefits; no one is arguing that they improve the availability or effects of creatine itself.

The major new benefit: increasing the efficiency of aerobic metabolism, and thus reducing fatigue. Citrate and pyruvate are both key steps in the aerobic-respiration pathway.

Why does aerobic metabolism matter to a lifter? One word: recovery. As in, recovery from one set to the next. Improve recovery and you improve your work capacity. Improve your work capacity and you can train longer and harder. Train longer and harder and you can get bigger and stronger.

Anaerobic exercise — a category that includes strength training, sprinting, and start-stop sports like basketball, tennis, and baseball — creates an oxygen debt, which has to be repaid by the heart. Your work capacity is limited by how well your aerobic energy system functions in restoring this oxygen debt.

A handful of studies have shown that citrate improves performance in high-intensity intervals as well as in endurance exercise. (22, 23) The evidence so far is encouraging, but not yet conclusive.

The picture for pyruvate at first appears a bit murky. In studies of people who took pyruvate for seven days, the researchers didn't detect any increases in blood levels of pyruvate, and didn't find improvements in exercise performance. (24, 25) On the other hand, long-term supplementation (4 weeks or more), at similar or even smaller doses, does increase pyruvate levels, and does improve anaerobic and aerobic performance. (26, 27, 28)

A recent study compared creatine citrate to creatine pyruvate head to head, using repeated sets of high-intensity work. (27) Both improved maximal strength during the first two or three intervals, compared to placebo. But only the subjects using creatine pyruvate continued to show performance gains throughout the course of 10 intervals.

In addition, pyruvate as a stand-alone supplement leads to greater weight loss in overweight individuals, along with greater increases in lean body mass. (29, 30, 31)

So if you're keeping score, here's what creatine pyruvate potentially offers:


Diet vs. Supplementation

Nobody reading T NATION regularly eats an "average" diet, but scientists don't study T NATION readers. So all we have to go on is this: an American eating an average diet gets about 1 gram of creatine per day. (8)

Fish is the best source of dietary creatine, followed by beef. Pork has some, while poultry has a negligible amount. (10)

Your body synthesizes another gram of creatine a day from amino acids, giving most people about 2 grams of creatine per day to work with. (8, 9)

As with protein, our bodies turn over creatine all day, every day. Our muscle, heart, and nerve cells are constantly breaking it down and rebuilding it, degrading about 2 grams per day in the process. (11, 12) As luck would have it, that's the same amount our bodies either produce or get from our food.

If we're going to increase our body's creatine stores by up to 40%, as mentioned earlier, we're going to have to get it from somewhere other than our dinner plate.

Even without supplements, some of us are closer to our max than others. If you load up on fish and beef, you're probably one of them. You can probably get away with smaller doses than someone like me, whose only source of meat is chicken, and I don't even get that every day.

Unfortunately, we don't have much research showing what happens if you take less than 3 grams per day. Studies typically use daily doses ranging from 3 to 10 grams. In those studies, regardless of whether they load or not, about 80% of participants achieve the maximum creatine concentration within a month. (5, 6, 7, 12)

The 20% of individuals who don't respond to 3 grams per day don't do any better with higher doses. (2) Why not? Maybe their bodies can't absorb it well. Maybe they excrete it too fast. Or maybe their muscles aren't as efficient at holding onto it. Or perhaps people who can't reach maximum creatine density have a higher proportion of Type 1 muscle fibers, which are more endurance-oriented and have less capacity for storing creatine. It's pure speculation, but it makes sense to me.

But let's get back to the central problem: An average person takes in 2 grams per day and loses 2 grams, and ends up with creatine stores that are about 40% below his maximum. What's the best way to fill up, with the least waste?

A study looking at urinary excretion of creatine and creatinine found that people who supplement with 5 grams per day excrete about 3 to 4 more grams per day than people who don't. So they're using 1 or 2 grams, and wasting the rest. (12)

No matter how much you take in, your body is going to lose about 1 to 2% of its stored creatine each day. So if you're that 200-pounder who wants to reach a total creatine capacity of 210 grams, instead of the 150 grams of someone who isn't supplementing, you won't be able to use more than about 4 grams of creatine from all sources each day.

Personally, I reach maximum benefit on a little less than a teaspoon per day, or just under 3 grams. I can't say that's the most anyone should take, but I think the research shows that anything beyond 5 grams per day for maintenance is overkill.

You can tell you're taking in too much if you find yourself peeing more than you normally do. This is a sign than the excess creatine is leaving your system, and taking water with it.


To Load or Not to Load

The standard loading protocol used in studies is 10 to 20 grams per day for three to five days, followed by a maintenance dose of 3 to 5 grams per day. Some studies omit the loading phase, and just go straight to 3 to 5 grams per day. Those who follow a loading protocol of 20 grams per day maximize their creatine concentration within two to three days. (13)

But 20 grams is a lot more than your body can absorb in a day, let alone for five straight days. A study I cited earlier shows that you lose about 8 grams on the first day. That goes up to 12 grams on the third day — more than half of your daily intake in the loading phase. (12)

People who forego the loading phase reach maximal concentration within about four weeks, at considerably less cost. (7) In the long term, there's no difference in benefits, and thus no need to load.

If you don't want to wait four weeks, a maximum loading dose of 10 grams per day for three to five days should work just fine. That's three level teaspoons or 2 heaping ones.

One possible downside to loading is that it probably increases your risk for side effects — diarrhea, bloat, cramps, dehydration, and even tendon tears. Anecdotal evidence certainly suggests that people who report these problems were taking higher doses, either as a loading phase or for maintenance. (14)


When to Take It

Pre-workout creatine will certainly increase your intravascular volume, and could help you get a bigger pump. But it can also pump up your GI tract, while the increased fluid in your veins could indicate intramuscular and tissue dehydration.

That's why I think creatine works best as part of your post-workout shake.


Using Creatine to Improve Your Physique and Performance

Most people using creatine for the first time will gain four to seven pounds within the first few weeks, if not the first few days. (2, 8, 18) This initial weight gain is almost entirely due to increased water retention within the muscles and blood vessels — more or less instant sarcoplasmic hypertrophy.

Some studies do report rapid increases in strength, along with the quick size gain. There are three possible reasons for this:


So, to sum it all up:

If you're currently using creatine, you're already convinced of its benefits. If you're not ... well, given what we know about its benefits as a sports supplement and a therapeutic agent, what are you waiting for?


References

1. Murray RK, et al. Harper's Biochemistry, 24th Edition. Stamford, CT: Appleton & Lange, 1996.

2. Lulinski B. Creatine Supplementation. 1999.

3. Wallner T. Kre-Alkalyn Buffered Creatine: Better Than Regular Creatine Monohydrate?. 2007.

4. Howard AN and Harris RC. Compositions Containing Creatine. 2007.

5. Harris RC, et al. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science (Colch) 83:367-374. 1992

6. Casey A, et al. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. American Journal of Physiology 271:E31-E37. 1996

7. Hultman E, et al. Muscle creatine loading in men. Journal of Applied Physiology 81:232-237. 1996

8. Persky AM and Brazeau GA. Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate. Pharmacological Reviews 53(2):161-176. 2001.

9. Wyss M and Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiology Reviews 80:1107-1213. 2000

10. Maughan R. Creatine supplementation and exercise performance. International Journal of Sport Nutrition 5:94-101. 1995.

11. Walker J. Creatine: Biosynthesis, regulation, and function. Adv Enzym 50:117-242. 1979

12. Vandenberghe K, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology 83: 2055-2063. 1997.

13. Terjung et al. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Medicine and Science of Sports and Exercise. 32: 706-717. 2000

14. Juhn MS and Tarnopolsky M. Potential side effects of oral creatine supplementation: A critical review. Clin J Sport Med 8: 298-304. 1998

15. Green AL, Hultman E, Macdonald IA, Sewell DA and Greenhaff PL. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. American Journal of Physiology 271E821-E826. 1996

16. Yokozawa T, et al. Comparison of toxic effects of methylguanidine, guanidinosuccinic acid and creatinine in rats with adenine-induced chronic renal failure. Nephron 51(3):388-92. 1989

17. Poortmans JR and Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medicine and Science of Sports and Exercise 31:1108-1110. 1999

18. Jenkins MA. Creatine Supplementation in Athletes. 1998

19. Creatine. 2009

20. Incledon T, Kreider RB. Creatine alpha-ketoglutarate is experimentally unproven. J Sports Med Phys Fitness 40(4):373-6. 2000.

21. Spillane M. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levelsJ Int Soc Sports Nutr. 6: 6. 2008

22. McNaughton L, et al. Sodium citrate ingestion and its effects on maximal anaerobic exercise of different durations. Eur J Appl Physiol Occup Physiol. 64:36—41. 1992

23. Potteiger JA, et al. Sodium citrate ingestion enhances 30 km cycling performance. Int J Sports Med. 1996

24. Ebersole KT, et al. The effect of pyruvate supplementation on critical power. J Strength Cond Res.14:132—134. 2000.

25. Morrison MA, et al. Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals. J Appl Physiol. ;89:549—556. 2000

26. Kalman D, et al. Effect of pyruvate supplementation on body composition and mood. Current Therapeutic Research. 59:793—802. 2000

27. Jäger R, et al. The effects of creatine pyruvate and creatine citrate on performance during high intensity exercise J Int Soc Sports Nutr. 5: 4. 2008

28. Ivy, JL. Effect of pyruvate and dihydroxyacetone on metabolism and aerobic endurance capacity. Medicine & Science in Sports & Exercise. 30(6):837-843. 1998.

29. Kalman D, et al. The effects of pyruvate supplementation on body composition in overweight individuals. Nutrition 15(5):337-340. 1999.

30. Kalman D, et al. Effect of pyruvate supplementation on body composition and mood. Current Therapeutic Research 59(11):793-802. 1998

31. Koh-Banerjee, et al. Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise. Nutrition 21(3):312-319. 2005



Catching Up On Creatine

By increasing work capacity, creatine allows you to lift more weight for more reps.

Catching Up On Creatine

Nobody on the planet knows more about monkey sex than Nik.

Catching Up On Creatine

Energy in the body is produced, stored, exchanged, and used through the mediator ATP.

Biotest German Creatine

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